Exploring the complex relationship between psychosocial stress and the gut microbiome: implications for inflammation and immune modulation.

There is growing interest in understanding the complex relationship between psychosocial stress and the human gastrointestinal microbiome (GIM). This review explores the potential physiological pathways connecting these two and how they contribute to a proinflammatory environment that can lead to the development and progression of the disease. Exposure to psychosocial stress triggers the activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary axis (HPA), leading to various physiological responses essential for survival and coping with the stressor. However, chronic stress in susceptible individuals could cause sustained activation of HPA and SNS, leading to immune dysregulation consisting of redistribution of natural killer (NK) cells in the bloodstream, decreased function of T and B cells, and elevation of proinflammatory cytokines such as interleukin-1, interleukin-6, tumor necrotic factor-α, interferon-gamma. It also leads to disruption of the GIM composition and increased intestinal barrier permeability, contributing to GIM dysbiosis. The GIM dysbiosis and elevated cytokines can lead to reciprocal effects and further stimulate the HPA and SNS, creating a positive feedback loop that results in a proinflammatory state underlying the pathogenesis and progression of stress-associated cardiovascular, gastrointestinal, autoimmune, and psychiatric disorders. Understanding these relationships is critical for developing new strategies for managing stress-related health disorders.